Stem Cell Injection in Cancer Survivors

This phase I, randomized, placebo-controlled, trial will evaluate the safety and feasibility
of allo-MSCs administered by transendocardial injection in thirty-six subjects with
anthracycline-induced cardiomyopathy (AIC). The first six subjects will receive allo-MSC
therapy (open label) and will be assessed for safety and feasibility of the study procedures.
Following 1 month data review of each of the six subjects by the National Heart, Lung, and
Blood Institute Gene and Cell Therapy Data Safety Monitoring Board; this will be followed by
a randomized, double-blind clinical trial enrolling thirty subjects. These thirty subjects
will be randomized 1:1 to receive allo-MSCs or placebo. All subjects will undergo cardiac
catheterization and study product administration using the NOGA Myostar catheter injection
system. Subjects will be followed at 1 day, 1 week, 1 month, 6 months, and 12 months post
study product injection. All endpoints will be assessed at the 6 and 12 month visits which
will occur 180 ±30 days and 365 ±30 days, respectively, after the day of study product
injection (Day 0).

For the purpose of the safety evaluations and endpoint analysis, the Investigators will
utilize an "intention-to-treat" study population. In addition, because this phase I study is
the first cell therapy study in this population, at 12 months all available standard-of-care
medical records for cancer surveillance will be reviewed for cancer recurrence.

Inclusion Criteria

To participate, a subject MUST:

1. Be ≥ 18 and < 80 years of age

2. Be a cancer survivor with diagnosis of AIC

3. Have an LVEF ≤ 45% by cMRI

4. Be in NYHA class II-III

5. Have received the initial diagnosis of AIC at least six months earlier and be on
stable, optimally-tolerated therapy with beta-blockers, ACE inhibitors/ARBs, and/or
aldosterone antagonists for 3 months, unless contraindicated

6. Have a period of at least two years of clinical cancer-free state* and low likelihood
of recurrence (a five-year risk of recurrence estimated at 30% or less), as determined
by an oncologist, based on tumor type, response to therapy, and negative metastatic
work-up at the time of diagnosis (*exceptions to this are carcinoma in situ or fully
resected basal and squamous cell cancer of the skin.)

7. Be a candidate for cardiac catheterization

Exclusion Criteria

To participate, a subject MUST NOT HAVE:

1. A life expectancy <12 months

2. A CT scan or baseline cardiac MRI showing new tumor or suspicious lymphadenopathy
raising concern of malignancy

3. Presence of obstructive CAD as determined via imaging within 5 years prior to study
enrollment provided there have been no symptoms or evidence of CAD since the test

4. Had a previous myocardial infarction

5. A history of radiation therapy AND evidence of constrictive physiology and/or evidence
of other patterns of non-ischemic cardiomyopathy on cardiac MRI (e.g., amyloidosis,
sarcoidosis, hemochromatosis, pure radiation-induced cardiomyopathy, etc.) not
consistent with AIC being the dominant etiology of heart failure

6. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2)
severe valvular (any valve) insufficiency/regurgitation within 12 months of consent.

7. Aortic stenosis with valve area ≤ 1.5cm2

8. A history of LV reduction surgery or cardiomyoplasty

9. Evidence of cardiogenic shock

10. A history of ischemic or hemorrhagic stroke within 90 days of baseline testing

11. Liver dysfunction during baseline testing, as evidenced by enzymes (e.g., AST, ALT,
alkaline phosphatase) greater than 3 times upper limit of normal

12. Diabetes with poorly controlled blood glucose levels (HbA1c > 8.5%)

13. An underlying autoimmune disorder or current immunosuppressive therapy (e.g., chronic
corticosteroid, rheumatologic or immune modulating therapy) or likelihood of use of
immunosuppressive therapy during participation in the trial (medications will be
considered on a case by case basis)

14. A baseline eGFR <35 ml/min/1.73m2

15. A contrast allergy that cannot adequately be managed by premedication

16. Received gene or cell-based therapy from any source within the previous 12 months

17. A hematologic abnormality during baseline testing as evidenced by hemoglobin < 9 g/dl;
hematocrit < 30%; absolute neutrophil count < 2,000 or total WBC count more than 2
times upper limit of normal; or platelet values < 100,000/ul

18. Evidence of active systemic infection at time of study product delivery

19. HIV and/or active HBV or HCV

20. Coagulopathy (INR > 1.5) not due to a reversible cause (e.g., warfarin and/or Factor
Xa inhibitors) (see Section 6.4 re: injection procedure and anticoagulation therapy)
Note: Subjects who cannot be withdrawn from anticoagulation will be excluded.

21. Presence of LV thrombus

22. Presence of a pacemaker and/or ICD generator with any of the following
limitations/conditions:

- manufactured before the year 2000

- leads implanted < 6 weeks prior to consent

- non-transvenous epicardial or abandoned leads

- subcutaneous ICDs

- leadless pacemakers

- any other condition that, in the judgment of device-trained staff, would deem an
MRI contraindicated

23. Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD
are not excluded)

24. A cardiac resynchronization therapy (CRT) device implanted < 3 months prior to consent

25. Other MRI contraindications (e.g. patient body habitus incompatible with MRI)

26. An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular
fibrillation or ventricular tachycardia within 30 days of consent

27. Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of
consent, or symptomatic Mobitz II or higher degree atrioventricular block without a
functioning pacemaker within 3 months of consent

28. A history of drug abuse (use of illegal "street" drugs except marijuana, or
prescription medications not being used appropriately for a pre-existing medical
condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical,
occupational, or legal problems arising from the use of alcohol or drugs within the
past 24 months

29. Cognitive or language barriers that prohibit obtaining informed consent or any study
elements (interpreter permitted)

30. Participation (currently or within the previous 30 days) in a cardiac related
investigational therapeutic (including stem cell based therapies) or device trial

31. Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling
to use acceptable forms of birth control during study participation

32. Any other condition that, in the judgment of the Investigator or Sponsor, would be a
contraindication to enrollment, study product administration, or follow-up